Our objective is to document changes associated with the early stage of osteoarthritis in dogs and to identify factors which modify the disease. Our aim is to examine the role of fibronectin in articular cartilage destruction at an early stage of the osteoarthritic process, before changes in joints can be detected by radiographic methods. We can study this aspect of the disease because of the advantages of the canine model, particularly the spontaneity of the disease, its predictability and expression in several joints of disease-prone dogs (hip, shoulder and knee joints), its slow onset, and our capacity to sample cartilage within and surrounding lesions as well as tissue from unaffected joints. The proposed studies would examine the mechanism for the recently observed increased content and synthesis of fibronectin in the abnormal cartilage of osteoarthritic joints. We want to localize the sites of accumulation of fibronectin using immunohistochemical methods at the electronmicroscopic level. We want to substantiate that fibronectin production is a useful and early marker of osteoarthritis and that its presence is consistent with the idea that chondrocytes from osteoarthritic cartilage have a changed phenotype. We wish to isolate chondrocytes from normal and osteoarthritic cartilage and determine in what ways they differ. We would compare the level of mRNA for fibronectin using available cDNA probes. We would also compare the cell size and shape, DNA content, position in the growth cycle, and the presence of fibronectin or its receptors on the cell surface using both established and novel methods of flow cytometry. Another, but related, aim is to ascertain how to manipulate the culture conditions of explants of "normal" cartilage in vitro in order to induce increased rates of fibronectin production. These proposed experiments taken together are designed to test the hypothesis that increased fibronectin production is a primary event in the pathogenesis and that chondrocytes from osteoarthritic cartilage are "dedifferentiated."